The technique, segmented retrograde intrabiliary injection (SRII), will be applied in the rat to study the effect of Amanita phalloides extract. Changes in recovery of metabolically inert marker compounds such as mannitol and sucrose will be used to assess permeability changes of the biliary tree. An increase in permeability would be indicated by decrease in recovery of these marker compounds in bile. Also intrabiliary pressure changes will be measured. These studies are based on the reports in the literature that phalloidin appears to increase the permeability of the liver as indicated by electron microscopic changes and biochemical changes. Our approach emphasized physiological changes to measure dynamic rather than static function. In another study, we will administer Triton X-100, a detergent, by SRII to locally damage the canalicular membrane. We feel this damage should increase the permeability of the canalicular membrane (measures as above). At the same time, we will measure the excretory function of the liver for carrier mediated transport for such drugs as bromphenol blue, ouabain and procaine amide ethobromide. Furthermore, we will see whether functions such as drug metabolism by the endoplasmic reticulum remain unaffected. Our aim is to demonstrate functional damage to the carrier mediated transport system located presumably at the canalicular membrane and obtain a clear separation from a simple diffusional process. More specific block of each carrier mediated process will subsequently be studied.